Albaconol Attenuates LPS-induced Macrophage Production Of Pro-inflammatory Cytokines By Suppressing NF-κB Activation

Albaconol is a new kind of prenylated resorcinols isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens. As a partial agonist of the vanilloid receptor, it has been shown that Albaconol induces contraction and desensitization of guinea pig trachea in vitro. Furthermore, Albaconol was reported to exhibit antitumor activity because it could inhibit the growth of human tumor cell lines including K562, A549, BGC823 and Bcap37, and the mechanisms for its antitumor effect may be related to its influence on the DNA topoisomerases.Macrophages represent a family of mononuclear leukocytes that are widely distributed throughout the body. As the first defense effector of host body, macrophages can recognize the invading microorganisms and eliminate the invaders. Also, the innate immune function of macrophages contributes to the activation of adaptive humoral and cellular immunity. In addition, macrophage is one of three kinds of professional antigen-presenting cells including dendritic cells, macrophages and B cells. Macrophages can produce many kinds of cytokines and inflammatory mediators, such as TNF- α , IL-1 β , IL-6 and NO which are involved in the defense functions and inflammation. So, macrophages are one of good target cells for immunosuppressive or anti-inflammatory drugs. Therefore, the primary aim of this study is to investigate the effects of Albaconol on the macrophage production of pro-inflammatory cytokines and its related mechanisms.We selected the murine macrophage cell line RAW264.7 as cellular model to observe the effect of Albaconol on the macrophage functions. By using MTT method to detect cell proliferation, we found that Albaconol inhibited proliferation of RAW264.7 cells in dose-dependent and time-dependent manners. The expressions of cytokines in RAW264.7 cells were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Resultsof RT-PCR showed that LPS-induced TNF- a , IL-6 and IL-1 P mRNA expressions were reduced in Albaconol-treated RAW264.7 cells compared to that in control cells. At the protein level as detected by ELISA, Albaconol also inhibited the LPS-induced production of TNF- a , IL-6 and IL-1 P in a dose-dependent manner. We also observed that the production of NO decreased in LPS-stimulated RAW264.7 cells after Albaconol treatment. Moreover, Albaconol could suppress the nuclear transcription factor NF-kB activation in LPS-stimulated RAW264.7 cells, accompanied with up-regulation of SOCS1 expression.In conclusion, these results demonstrate that a natural compound Albaconol inhibits LPS-induced macrophage production of pro-inflammatory cytokines by suppressing NF-kB activation and up-regulating SOCS1 expression, indicating that Albaconol may be a candidate of immunosuppressive and anti-inflammatory drugs. However, whether or not Albaconol possesses pharmacological and therapeutic effects needs further extensive investigation.